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2.
Mymensingh Med J ; 33(1): 267-278, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163803

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is a pathology seen not only in precelampsia with severe symptoms and eclampsia but in a varicty of diseases/ conditions. With the availability of neuroimaging, it is possible to know the exact underlying Central nervous system (CNS) pathology in preeclampsia with severe symptoms and eclampsia and thus therapy can be targeted. Preeclampsia with severe symptoms and eclampsia remains to be an important cause of maternal morbidity and mortality in both the developing and developed world. The objective of this study was to evaluate the association of Posterior reversible encephalopathy syndrome (PRES) by MRI (Magnetic resonance imaging) with preeclampsia with severe symptoms and eclampsia in south east part of Bangladesh. This cross-sectional observational study was performed among women suffering from preeclampsia with severe symptoms and eclampsia who attended at Obstetrics & Gynaecology department of Chittagong Medical College Hospital (CMCH), Bangladesh from January 2021 to June 2021. According to inclusion/exclusion criteria 50 samples were taken by convenient sampling for this study. A detail history was taken and complete general physical and gynecological examination was performed. Required data was collected through preset questionnaire. Neuroimaging reports were reviewed by both neurologist and radiologist. Data was analyzed by using windows based computer software device, SPSS 25.0. Results obtained from this study will be used to make a statement regarding aggressive management for cerebral vasospasm in severe preeclampsia and eclamptia related PRES. PRES has been reported to be reversible but late recognition or incorrect treatment can cause irreversible brain damage. Institution of early treatment leads to resolution of symptoms without any neurologic deficit and thus reduces maternal morbidity and mortality. PRES is a cliniconeuroradiologic entity. This study can aware doctors regarding prompt diagnosis of PRES in peripartum period among patient suffering from preeclampsia with severe symptoms and eclampsia by imaging aside clinical findings. A conclusive decision can be made to improve the outcome in this potentially life threatening but reversible condition.


Assuntos
Eclampsia , Síndrome da Leucoencefalopatia Posterior , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Eclampsia/terapia , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Bangladesh/epidemiologia , Estudos Transversais
3.
Mymensingh Med J ; 31(4): 1020-1026, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36189547

RESUMO

Meningitis literally means inflammation of the meninges. It is mostly caused by bacteria, virus, fungus and protozoa and pyogenic meningitis constitutes a serious neurological disorder associated with significant morbidity and mortality in developing countries. This study was carried out to evaluate the clinical presentation and immediate outcome of pyogenic meningitis in children. This was a prospective observational study and conducted at department of Paeditrics in Cumilla Medical College Hospital, Cumilla, Bangladesh from July 2014 to June 2015. Total 50 children were diagnosed as pyogenic meningitis fulfilling the inclusion criteria was included in this study. Cases were enrolled purposively. Immediately after admission through history and clinical examination, complete blood count, random blood sugar, Cerebrospinal fluid (CSF) examination and blood culture was done in all patients. For statistical analysis chi-square test was done and significance of analysis was made when p value <0.05. This study includes patients aged between 2 months to 12 years and male female ratio was 1.5:1. Several risk factors like male sex (60.0%), age below one year (42.0%), Protein energy malnutrition (PEM) (30.0%), not exclusively breastfed (44.0%) were identified. Common presenting complaints were fever (100.0%), convulsion (96.0%), altered consciousness (42.0%) and vomiting (38.0%). Common physical signs were neck rigidity (56.0%), Kernig's sign (26.0%) and bulged fontanelle (34.0%). CSF was hazy in 54.0%, clear in 38.0% and turbid in 08.0% cases, CSF protein was more than 100mg/dl in 90.0% of the cases and glucose was less than 40mg/dl in most of the cases (94.0%). Streptococcus Pneumoniae (49.0%) followed by Neisseria Meningitidis (38.0%) were the two most commonly isolated organism responsible for pyogenic meningitis. Mortality rate during hospital stay was 18.0% and complications developed in 18.0% of cases. To avoid maltreatment in our resource limited setting due to failure of identifying organism, this study might help to administer appropriate antibiotics against organism and to reduce morbidity and mortality in meningitis. This study revealed less mortality rate in our country than neighbors and severe malnutrition important risk factors for the burden of pyogenic meningitis. It requires large scale multicentre studies to establish the whole scenario of Bangladesh.


Assuntos
Glicemia , Meningites Bacterianas , Antibacterianos/uso terapêutico , Criança , Feminino , Febre , Humanos , Lactente , Masculino , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/epidemiologia , Estudos Prospectivos
4.
Colloids Surf B Biointerfaces ; 154: 421-428, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28388528

RESUMO

Synthesis and characterization of nano-structured porous granules, with fairly defined morphology and porosity, is crucial because such granules are widely utilized for various technological applications. However, an easy, one-step, economic synthesis protocol for large scale production is extremely desirable. In the present work, we have reported the synthesis and characterization of the nano-structured micro-granules using aerosol drying of bi-colloidal suspension of nano-silica and milk. Removal of soft organic component from the granules results in formation of meso and macro pores with moderate specific surface area. Granule morphology and porosity depends strongly on the concentration ratio of the individual components in the drying aerosol as well as the interaction between them.


Assuntos
Leite/química , Nanoestruturas/química , Nanotecnologia/métodos , Dióxido de Silício/química , Aerossóis , Animais , Coloides , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Porosidade , Propriedades de Superfície , Suspensões
5.
Langmuir ; 32(10): 2464-73, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26900937

RESUMO

Understanding how a tiny dilute evaporative colloidal spray droplet gets transformed into a microgranule with a characteristic morphology is crucial from scientific as well as technological points of view. In the present work, it is demonstrated that the morphology and the size distribution of the microcapsules can be tuned simply by adjusting the drying temperature. Shape and size of the capsules are quantified at four different drying temperatures. It is shown that the morphology transits gradually from sphere to toroid with increasing temperature keeping the average volume-fraction of the correlated nanoparticles nearly unaffected for the synthesized granules. A plausible mechanism for the chronological pathway of such morphological transformation is illustrated. Computer simulation corroborates the experimentally observed morphological transition. The variation in hollowness and buckling tendency of the capsules are elucidated by scattering and imaging techniques.

6.
Carbohydr Polym ; 124: 77-84, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-25839796

RESUMO

Guar gum based nano-composite films were prepared using organically modified (cloisite 20A) and unmodified (nanofil 116) nanoclays. Effect of nanoclay incorporation on mechanical strength, water vapor barrier property, chromatic characteristics and opacity of films was evaluated. Nano-composites were characterized using X-ray scattering, FTIR and scanning electron microscopy. A nanoclay concentration dependent increase in mechanical strength and reduction in water vapor transmission rate was observed. Films containing nanofil 116 (2.5% w/w guar gum) and closite 20A (10% w/w guar gum) demonstrated a 102% and 41% higher tensile strength, respectively, as compared to the control. Lower tensile strength of cloisite 20A films as compared to nanofil 116 films was due to its incompatibility with guar gum. X-ray scattering analysis revealed that interstitial spacing between nanofil 116 and cloisite 20A sheets increased due to intercalation by guar gum polymer. This resulted in improved mechanical and barrier properties of nano-composites compared to control.


Assuntos
Galactanos/química , Mananas/química , Nanocompostos/química , Gomas Vegetais/química , Resistência à Tração , Microscopia Eletrônica de Varredura , Espalhamento de Radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Vapor , Difração de Raios X
7.
Langmuir ; 31(16): 4612-8, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25839830

RESUMO

In-situ scanning small-angle X-ray scattering (SAXS) experiments have been performed to probe the drying of a single suspended droplet of silica colloids. It has been demonstrated that the formation of a nanoparticle shell during drying can be confirmed just by measuring the temporal evolution of the spatial transmission profile across the drying droplet. The shrinkage of the droplet stops once the shell is formed. The temporal dependence of the shell thickness and droplet radius has been estimated by quantitative analysis of the functionality of the transmission profiles. It is revealed that the position of the correlation peak originating from interactions between silica nanoparticles evolves linearly during the initial stage of drying and exhibits sigmoidal growth behavior in later stages. The interaction between colloidal particles in different drying stages has been investigated. We provide experimental confirmation of the transition from repulsive interaction to a capillary-driven short-range attraction during shell formation. The present work demonstrates that in-situ scanning SAXS on a suspended droplet is an invaluable technique for monitoring the dynamic self-organization of colloids as it probes the drying of complex fluids without the interference of a substrate.

8.
Colloids Surf B Biointerfaces ; 127: 164-71, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25677340

RESUMO

We have synthesized nano-structured silica-Escherichia coli composite micro-granules by spray drying of mixed suspension of silica and E. coli through evaporation-induced assembly. Synthesized micro-granules were subjected to calcination in order to form shape-matched macro-pores by removing the bacterial cells. The optimization of calcination temperature is crucial because calcination process leads to two contrasting effects, namely, (i) removal of E. coli from the granules and (ii) alteration of mesoscopic structure in the silica network. We have used small-angle neutron scattering and thermo-gravimetric analysis to determine the optimum temperature for calcination of these granules. It was found that calcination in the temperature range of 200°C to 400°C removes the cells without significant alteration of the nano-structured silica network. However, beyond 500°C, calcination results significant coalescence between the silica particles. Calcination at 600°C eventually collapses the meso-pore network of silica interstices.


Assuntos
Escherichia coli/fisiologia , Nanoestruturas/química , Nanotecnologia/métodos , Dióxido de Silício/química , Temperatura , Escherichia coli/ultraestrutura , Nanoestruturas/ultraestrutura , Difração de Nêutrons , Espalhamento a Baixo Ângulo , Termogravimetria , Difração de Raios X
9.
Cell Death Dis ; 6: e1593, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25590803

RESUMO

Overexpression of anti-apoptotic BCL-2 family members is a hallmark of many lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) that can be targeted with small molecule inhibitors. ABT-199 is a rationally designed BCL-2 homology (BH)-3 mimetic that specifically binds to BCL-2, but not to MCL-1 and BCL-xL. Although the thrombocytopenia that occurs with navitoclax treatment has not been a problem with ABT-199, clinical trials in CLL could benefit by lowering the ABT-199 concentration through targeting other survival pathways. In this study, we investigated the mechanisms of resistance that develops to ABT-199 therapy by generating ABT-199-resistant (ABT199-R) cell lines via chronic exposure of NHL cell lines to ABT-199. Acquired resistance resulted in substantial AKT activation and upregulation of MCL-1 and BCL-xL levels that sequestered BIM. ABT199-R cells exhibited increased MCL-1 stability and failed to activate BAX in response to ABT-199. The ABT-199 acquired and inherent resistant cells were sensitized to treatment with ABT-199 by inhibitors of the PI3K, AKT, and mTOR pathways, NVP-BEZ235 and GS-1101. NVP-BEZ235, a dual inhibitor of p-AKT and mTOR, reduced MCL-1 levels causing BIM release from MCL-1 and BCL-xL, thus leading to cell death by BAX activation. The PI3Kδ inhibitor GS-1101 (idelalisib) downregulated MCL-1 and sensitized ABT199-R cells through AKT-mediated BAX activation. A genetic approach, through siRNA-mediated down-regulation of AKT, MCL-1, and BCL-xL, significantly decreased cell survival, demonstrating the importance of these cell survival factors for ABT-199 resistance. Our findings suggest a novel mechanism that modulates the expression and activity of pro-survival proteins to confer treatment resistance that could be exploited by a rational combination therapeutic regimen that could be effective for treating lymphoid malignancies.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma/enzimologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteína bcl-X/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Linfoma/genética , Linfoma/patologia , Proteínas de Membrana/metabolismo , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Purinas/farmacologia , Quinazolinonas/farmacologia , Quinolinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Regulação para Cima/efeitos dos fármacos , Proteína bcl-X/genética
10.
Free Radic Res ; 49(3): 253-68, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25564263

RESUMO

In this study, we report the synthesis of four 2-(arylazo)phenol-Pd(II) complexes and their anti-proliferative property against the human lung cancer (A549), cervical cancer (HeLa), and ovarian teratocarcinoma (PA-1) cell lines with cisplatin as the gold standard. One of the complexes, [Pd(L(2))2], induced robust apoptosis in all the chosen cells, as revealed by annexin-V-positive/propidium iodide dual staining, increased sub-G1 cell cycle population, and significant morphological changes in the treated cells. The Pd complex inflicted mitochondrial dysfunction leading to mitochondrial membrane potential loss, reactive oxygen species generation and release of cytosolic cytochrome c that activated caspase-9 and caspase-3 proteins which finally caused programmed cell death.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Paládio/farmacologia , Fenóis/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Complexos de Coordenação/química , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Paládio/química , Fenóis/química
11.
Phys Chem Chem Phys ; 17(2): 911-7, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25407300

RESUMO

The rate coefficients for the reactions of Cl((2)PJ) with methylamine (R1), dimethylamine (R2) and trimethylamine (R3) have been measured using the laser flash photolysis - resonance fluorescence technique as a function of temperature (274-435 K) and pressure (25-400 Torr N2). The experimental data are well-represented by the following temperature- and pressure-independent rate coefficients (10(10) × k/cm(3) molecule(-1) s(-1)): kR1 = 2.90 ± 0.44, kR2 = 3.89 ± 0.58, kR3 = 3.68 ± 0.55; the uncertainties are estimates of accuracy at the 95% confidence level. Potential energy surfaces (PES) for the reactions have been characterized at the MP2/cc-pVTZ level and improved single point energies of stationary points obtained in CCSD(T)-F12a calculations. The PES for all reactions are characterized by the formation of pre and post reaction complexes and submerged barriers. Rate coefficients for the reactions were calculated as a function of temperature and pressure using a master equation model based on the coupled cluster theory results. The calculated rate coefficients are in good agreement with experiment; the overall rate coefficients are relatively insensitive to variations of the barrier heights within typical chemical accuracy, but the predicted branching ratios vary significantly. The inclusion of tunnelling has no effect.

12.
J Phys Chem B ; 119(1): 212-8, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25496449

RESUMO

Assembled diglycolamides (DGAs) have a strong affinity toward f-element ions at high nitric acid concentrations. Small angle X-ray scattering studies revealed that nitric acid concentration dependent changes occur in the geometrical arrangement of the DGA units of monomeric methacryloyl-DGA and the corresponding polymeric DGA. Cylindrical aggregates of methacryloyl-DGA were formed in 10:1 n-dodecane:1-decanol (added for solubility reasons) upon equilibration with nitric acid. The lengths and diameters of the cylindrical methacryloyl-DGA aggregates increased on varying the nitric acid concentration from 3 to 4 mol L(-1). This resulted in an increase of the distribution coefficient (D) of Eu(3+) ions from 72 to 197. The physical structure of cross-linked (10 mol %) poly(methacryloyl-DGA) reorganized distinctly upon equilibration with nitric acid. In this case, also the DEu(3+) values increased significantly from 147 mL g(-1) at 1 mol L(-1) HNO3 to ∼4000 mL g(-1) at 4 mol L(-1) HNO3. Hydrogen bonds between the outer sphere of Eu(3+)/Am(3+)/Pu(4+) nitrate and DGA units provide stabilization in the hydrophobic environment. This results in enhancement of their extraction upon increasing nitric acid concentration both in the organic phase as well as in the polymer matrix. Though monomeric and polymeric methacryloyl-DGA are different in their physical assembling, the normalized DI values for a same f-element ion upon varying HNO3 concentrations show remarkably similar patterns in both forms. In addition, the unusual stoichiometry deduced from the slopes of the log D vs log[HNO3] curves at fixed nitrate concentration seems to suggest that the normal extraction mechanism may not be operating in the hydrogen bonded DGA assemblies.

13.
Soft Matter ; 10(10): 1621-7, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24651879

RESUMO

Colloidal particles in a tiny drying droplet are forced to assemble due to attractive capillary forces. Jamming of the particles throughout the droplet remains either isotropic or anisotropic depending upon the drying kinetics and the physicochemical environment. In this work, we explore the dynamical evolution of such an assembly process across a single evaporative droplet by in situ scanning small-angle scattering using a micro-focused X-ray beam at the synchrotron source. A methodology has been elucidated to differentiate quantitatively between the isotropic and the anisotropic jamming process. Switching of jamming behaviour depending on the initial particle volume fraction in the droplet has been demonstrated. Three distinct stages of assembly, associated with droplet shrinkage, have been revealed even during isotropic jamming. This is in contrast to the drying of a pure liquid droplet under diffusion limited evaporation. It has been established that such in situ scattering measurements can also be used to estimate the temporal evolutions of the viscosity of a drying suspension as well as the diffusivity of nanoparticles in a droplet.

14.
Langmuir ; 30(9): 2460-9, 2014 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-24533743

RESUMO

We demonstrate for the first time the intrinsic role of nanoconfinement in facilitating the chemical reduction of metal ion precursors with a suitable reductant for the synthesis of metal nanoparticles, when the identical reaction does not occur in bulk solution. Taking the case of citrate reduction of silver ions under the unusual condition of [citrate]/[Ag(+)] ≫ 1, it has been observed that the silver citrate complex, stable in bulk solution, decomposes readily in confined nanodomains of charged and neutral matrices (ion-exchange film and porous polystyrene beads), leading to the formation of silver nanoparticles. The evolution of growth of silver nanoparticles in the ion-exchange films has been studied using a combination of (110m)Ag radiotracer, small-angle X-ray scattering (SAXS) experiments, and transmission electron microscopy (TEM). It has been observed that the nanoconfined redox decomposition of silver citrate complex is responsible for the formation of Ag seeds, which thereafter catalyze oxidation of citrate and act as electron sink for subsequent reduction of silver ions. Because of these parallel processes, the particle sizes are in the bimodal distribution at some stages of the reaction. A continuous seeding with parallel growth mechanism has been revealed. Based on the SAXS data and radiotracer kinetics, the growth mechanism has been elucidated as a combination of continuous autoreduction of silver ions on the nanoparticle surfaces and a sudden coalescence of nanoparticles at a critical number density. However, for a fixed period of reduction, the size, size distribution, and number density of thus-formed Ag nanoparticles have been found to be dependent on physical architecture and chemical composition of the matrix.

16.
Phys Chem Chem Phys ; 16(4): 1399-408, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24296912

RESUMO

Carbon based nanofillers have shown phenomenal improvements in thermo-mechanical properties of poly vinyl alcohol (PVA) based nanocomposites depending on their interaction with PVA molecules and dispersion in the polymer matrix. In the present study, PVA based nanocomposites with amino-functionalized multi-wall carbon nanotubes (fMWCNTs, 0.2, 0.4, 0.8 and 1.0 wt%) were prepared by a simple casting method from aqueous solution. The relative increase in Young's modulus with 0.4% fMWCNTs was observed to be comparable with that for PVA-nanodiamond composite films which have been shown to have higher strength compared to nanotube and graphene oxide based nanocomposites. In order to investigate the nanolevel molecular packing (sub-nano level free volumes and nano level lamellar structure) and its role in thermal and mechanical properties, positron annihilation spectroscopy and small angle scattering have been used. The crystallinity and morphology of the samples were characterized using X-ray diffraction and scanning electron microscopy. The studies showed that interfacial interaction between PVA molecules and functionalities on the surface of fMWCNTs results in the formation of an ordered structure of PVA molecules which enhances load transfer between the PVA matrix and fMWCNTs leading to improved mechanical properties. The thermal properties of the composites were observed to be unaffected at the studied filler concentration.

17.
Carbohydr Polym ; 98(2): 1610-7, 2013 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-24053847

RESUMO

Mechanical and water vapor barrier properties of biodegradable films prepared from radiation processed guar gum were investigated. Films prepared from GG irradiated up to 500 Gy demonstrated significantly higher tensile strength as compared to non-irradiated control films. This improvement in tensile strength observed was demonstrated to be due to the ordering of polymer structures as confirmed by small angle X-ray scattering analysis. Exposure to doses higher than 500 Gy, however, resulted in a dose dependent decrease in tensile strength. A dose dependent decrease in puncture strength with no significant differences in the percent elongation was also observed at all the doses studied. Water vapor barrier properties of films improved up to 15% due to radiation processing. Radiation processing at lower doses for improving mechanical and barrier properties of guar based packaging films is demonstrated here for the first time.


Assuntos
Embalagem de Alimentos , Galactanos/efeitos da radiação , Mananas/efeitos da radiação , Gomas Vegetais/efeitos da radiação , Água/química , Relação Dose-Resposta à Radiação , Galactanos/química , Mananas/química , Permeabilidade , Gomas Vegetais/química , Radiação Ionizante , Espalhamento a Baixo Ângulo , Vapor , Resistência à Tração , Difração de Raios X
18.
Cell Death Dis ; 4: e628, 2013 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-23681223

RESUMO

The purine analog fludarabine (Fd) is an essential therapeutic for chronic lymphocytic leukemia (CLL). Innate or acquired resistance to Fd is a significant clinical problem and is largely mediated by increased expression of BCL-2 family members. The antiapoptotic BCL-2 family proteins inhibit both apoptosis and autophagy, therefore, downregulation of antiapoptotic BCL-2 family proteins and enhanced autophagy must coexist in cells dying in response to an apoptosis inducing therapeutic. However, in the drug-resistant cells that have an increased dependence on antiapoptotic proteins, whether autophagy is also inhibited remains unclear. Here, we examined the role of the BCL-2 family in regulating cell death and autophagy in leukemic cell lines and their derivative isogenic Fd-resistant (FdR) cells. MCL-1 degradation following Fd treatment freed the proapoptotic effectors BIM and BECN1, thus leading to cell death-associated autophagy in Fd-sensitive cells. However, in FdR cells, low BIM expression and BECN1 sequestration by MCL-1 prevented cell death. Consistently, in sensitive cells inhibition of apoptosis using siBIM and of both the early-phase autophagy nucleation steps by siBECN1, shATG7 or 3-methyladenine and the late-phase autophagy by shLAMP2, significantly reduced Fd-induced cell death. Paradoxically, FdR cells were addicted to basal autophagy, which was dependent on AMP-activated protein kinase (AMPK) but not BECN1. Moreover, in FdR cells, inhibition of autophagy by shLAMP2, but not siBECN1, enhanced cell death. The BH3-mimetic obatoclax released BIM and BECN1 from MCL-1 in Fd-sensitive and BECN1 from MCL-1 in FdR cells, and was effective at killing both Fd-sensitive and - resistant leukemic cells, including primary CLL cells. Therefore, a differential regulation of autophagy through BECN1 and AMPK signaling in Fd-sensitive and - resistant cells determines the different possible outcomes of autophagy inhibition. These findings suggest effective means to overcome Fd resistance by induction of BIM-dependent apoptosis and activation of BECN1-dependent autophagy.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Vidarabina/análogos & derivados , Proteínas Quinases Ativadas por AMP/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Proteína 7 Relacionada à Autofagia , Proteína 11 Semelhante a Bcl-2 , Proteína Beclina-1 , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Proteína 2 de Membrana Associada ao Lisossomo/antagonistas & inibidores , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides , Ligação Proteica , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo , Vidarabina/farmacologia , Vidarabina/uso terapêutico
19.
Langmuir ; 28(31): 11343-53, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22794199

RESUMO

The evaporation-induced self-assembly of mixed colloids has been employed to synthesize microspheres of TiO(2)/SiO(2) nanocomposites. Small-angle neutron/X-ray scattering and scanning electron microscopy experiments reveal the hierarchical morphology of the microspheres. Although the internal structure of the microspheres, consisting of solely silica nanoparticles, gets significantly modified with time because of the reduction in the high specific surface area by internal coalescence, the same for the composite microspheres remains stable over an aging time of 1 year. Such temporal stability of the composite microspheres is attributed to the inhibition of coalescence of the silica nanoparticles in the presence of titania nanoparticles. X-ray diffraction and thermogravimetric results show the improved thermal stability of the composite grains against the anatase-to-rutile phase transition. Such thermal stability is attributed to the suppression of the growth of titania nanoparticles in the presence of silica nanoparticles. The UV-vis results indicate the confinement effect of the TiO(2) nanoparticles in the silica matrix. A plausible mechanism has been elucidated for the formation of microspheres with different morphology during self-assembly.

20.
Langmuir ; 28(3): 1914-23, 2012 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-22185181

RESUMO

Micrometric grains of anisotropic morphology have been achieved by evaporation-induced self-assembly of silica nanoparticles. The roles of polymer concentration and its molecular weight in controlling the buckling behavior of drying droplets during assembly have been investigated. Buckled doughnut grains have been observed in the case of only silica colloid. Such buckling of the drying droplet could be arrested by attaching poly(ethylene glycol) on the silica surface. The nature of buckling in the case of only silica as well as modified silica colloids has been explained in terms of theory of homogeneous elastic shell under capillary pressure. However, it has been observed that colloids, modified by polymer with relatively large molecular weight, gives rise to buckyball-type grains at higher concentration and could not be explained by the above theory. It has been demonstrated that the shell formed during drying of colloidal droplet in the presence of polymer becomes inhomogeneous due to the presence of soft polymer rich zones on the shell that act as buckling centers, resulting in buckyball-type grains.

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